Camptothecin-1-oxide derivatives

Abstract

New 5- and/or 7-substituted camptothecin-1-oxide derivatives possessing anti-tumor activity with slight toxicity, represented by the general formula: ##STR1## wherein R is a hydrogen atom, an alkyl group, a hydroxyl group, an alkoxy group or an acyloxy group and R' is a hydrogen atom, an alkyl group, an aralkyl group, a hydroxymethyl group, an acyloxymethyl group or a carboxymethyl group, with the proviso that both of R and R' should not be hydrogen atoms. These 5- and/or 7-substituted camptothecin-1-oxide derivatives are prepared by treating the corresponding 5- and/or 7-substituted camptothecins with a peroxidant as an N-oxidizing reagent.

What is claimed is: 
     
       1. A 5- or 7-substituted camptothecin-1-oxide derivative of the formula: ##STR6## wherein R is a hydrogen atom, a straight or branched C 1  -C 30  alkyl group, a C 5  -C 7  cycloalkyl group, a hydroxyl group, a C 1  -C 30  alkoxy group or a C 1  -C 18  acyloxy group and R 1  is a hydrogen atom, a C 1  -C 30  alkyl group, a phenylalkyl group, a naphthylalkyl group, a hydroxymethyl group, a C 1  -C 18  acyloxymethyl group or a carboxymethyl group, with the proviso that both R and R 1  are not hydrogen. 
     
     
       2. A 5-alkylcamptothecin-1-oxide having 1 to 18 carbon atoms in the alkyl group thereof. 
     
     
       3. A 5-alkoxycamptothecin-1-oxide having 1 to 18 carbon atoms in the alkoxy group thereof. 
     
     
       4. A 7-alkylcamptothecin-1-oxide having 1 to 18 carbon atoms in the alkyl group thereof. 
     
     
       5. A 7-aralkylcamptothecin-1-oxide derivative wherein the aralkyl group is selected from the group consisting of benzyl, phenethyl, phenylpropyl and 1-naphthylmethyl. 
     
     
       6. A 7-acyloxymethylcamptothecin-1-oxide oxide having 1 to 18 carbon atoms in the alkyl group thereof. 
     
     
       7. 7-Hydroxymethylcamptothecin-1-oxide. 
     
     
       8. A 5- or 7-substituted camptothecin-1-oxide derivative as in claim 1, wherein the alkyl group contains from 1 to 18 carbon atoms, the alkoxy group contains from 1 to 8 carbon atoms and the acyl group contains from 1 to 8 carbon atoms.